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Lessons Learned: Dose Selection of Small Molecule-Targeted Oncology Drugs

Julie M Bullock1, Atiqur Rahman2, Qi Liu3

  • 1d3 Medicine LLC, Parsippany, New Jersey.

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
|June 3, 2016
PubMed

Insights

Determining the right drug dose is crucial in cancer treatment. The traditional maximum tolerated dose (MTD) approach is less effective for new targeted cancer therapies, necessitating alternative dose and exposure strategies.

Area of Science:

  • Oncology
  • Pharmacology
  • Drug Development

Background:

  • Dose evaluation is critical for oncology drug development.
  • Phase I trials traditionally determine the maximum tolerated dose (MTD) for subsequent studies.
  • The MTD approach, suitable for cytotoxics, is problematic for novel small molecule-targeted agents.

Discussion:

  • This review critically examines the limitations of the MTD in modern oncology drug development.
  • It explores alternative strategies for dose and exposure exploration in targeted therapies.
  • Lessons learned from recent targeted oncology agent approvals are discussed.

Key Insights:

  • The MTD is an outdated metric for determining optimal Phase II doses for targeted cancer therapies.
  • Dose and exposure exploration offers a more promising approach for these agents.
  • Adapting dosing strategies is essential for advancing targeted oncology drug development.

Outlook:

  • Future oncology development programs should prioritize adaptive dosing and exposure-based strategies.
  • Further research into novel dose-finding methodologies is warranted.
  • Successful implementation of new dosing strategies will enhance the efficacy and safety of targeted cancer agents.

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